The Biliary System

Gallbladder Anatomical Variants

Agenesis of the gallbladder is extremely rare, with a prevalence of 0.03%–0.07%. A double gallbladder occurs in about 0.03%, usually with a shared cystic duct, and the accessory gallbladder is often diseased.

True gallbladder septa are uncommon and, when occurring at the fundus, form a Phrygian cap. Frequently, an apparent septum is merely gallbladder wall folding, which can vary with patient position.

The gallbladder can be abnormal in position, being retrohepatic, suprahepatic, left-sided or intrahepatic, the latter potentially presenting as a liver abscess if complicated by acute cholecystitis. A number of forms of left-sided gallbladder exist:

• 1.

  The gallbladder lies under the left hepatic lobe to the left of the falciform ligament

• 2.

  Independent development of a second gallbladder from the left hepatic duct with regression or failure of development of a right gallbladder

• 3.

  Herniation of the gallbladder through the foramen of Winslow

• 4.

  Transposition of the viscera.

Ultrasound

Transabdominal ultrasound (US) is frequently the first imaging technique employed for patients presenting with hepatobiliary-type symptoms as it is more accurate than Computed tomography (CT) for diagnosing acute biliary, especially gallbladder, disease. Imaging is usually performed following a 4-hour fast, allowing the gallbladder to fill and reducing obscuring upper abdominal gas. The wall of a normal non-contracted gallbladder is less than 3 mm thick and is smooth. US allows a dynamic assessment and by moving the patient helps differentiate stones, sludge and polyps. Doppler US allows assessment of vascularity, while focal gallbladder tenderness can be determined using probe pressure. The normal cystic duct may not be visible; however, the extrahepatic bile duct can be seen as a tubular structure anterior to the portal vein and lacking blood flow on Doppler.

Contrast-enhanced US (CEUS) using second-generation microbubble agents can be performed at transabdominal, endoscopic and intraoperative US.

CEUS is achieved by the use of intravenous (IV) injection of very small volumes of microbubbles comprising an inert gas contained by a stabilising shell. The small bubble size allows passage through the pulmonary to the systemic circulation. The bubbles resonate on low-power US insonation, generating harmonic frequencies, the display of which can be separated from the fundamental image in a way analogous to digital subtraction angiography. Most agents are purely intravascular and are therefore blood pool agents. The bubbles gradually break down safely with insonation, and one injection allows diagnostic enhancement for approximately 5 to 8 minutes. The microbubbles are extremely strong signal enhancers compared with CT and magnetic resonance imaging (MRI) contrast agents, and the use with real-time US allows very high spatial and temporal resolution. They have a very high safety profile and can be used in the presence of renal impairment and cardiac pacemakers, both significant advantages over CT and MRI.

CEUS is useful in selected patients: for example, in differentiating sludge from tumour, identifying perforation in cholecystitis and better demonstrating hilar cholangiocarcinoma.

Computed Tomographic Cholangiography

Computed tomographic intravenous cholangiography (CT-IVC) relies on an infusion of iodinated contrast agent, such as sodium ipodate, which undergoes biliary excretion. CT is performed around 30 minutes after the infusion, allowing high-resolution reformatted images to be obtained. Prone imaging may be performed after supine images if intraductal gas is present or contrast is layering. As a functional imaging technique, the presence of contrast agent within the duodenum proves that the biliary tree does not have a complete obstruction. This functional information also allows the direct demonstration of bile leaks, biliary communication with cysts and segmental obstruction, which is not obtained with routine non-contrast magnetic resonance cholangiopancreatography (MRCP). Unfortunately access to CT-IVC is reliant on access to the contrast agent that is becoming more limited. CT-IVC and MRCP are complementary investigations, with both offering case-dependent advantages.

Sodium iotroxate is safer than older IV biliary agents, with reported complications in 3.5% of patients (3.0% minor, 0.3% moderate and 0.2% severe) and an estimated mortality rate of 0.005%.

Adequate excretion of contrast agent relies on near-normal hepatocyte function, so the technique is of no value in the investigation of jaundice, and usually fails if bilirubin levels are more than about two times normal.

Magnetic Resonance Cholangiopancreatography

MRCP has substantially replaced diagnostic percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP). It relies on heavily T ₂ weighted sequences that display stationary water as high signal. Multiplanar thin and thick section acquisitions are obtained using fast spin-echo techniques. As conventional MRCP is not reliant on excretion of contrast material, it is suitable for jaundiced patients, a clear advantage compared with CT-IVC.

More recently, MR has been combined with hepatobiliary contrast agents. These agents, which include gadobenate dimeglumine and gadoxetic acid disodium, shorten T ₁ relaxation, providing positive contrast images on T ₁ weighted sequences. Biliary excretion can occur as early as 10 minutes after injection, depending upon liver function, although often images are obtained after 30 minutes. The contrast agent provides functional as well as anatomical information but, as with CT-IVC, depends on near-normal excretory hepatocyte function. As T ₁ weighted MR sequences are used, it is possible to use near-isotropic three-dimensional gradient-echo acquisitions. Contrast-enhanced MR cholangiography using hepatobiliary contrast agents has similar applications to CT-IVC, except that it seldom produces the high spatial and contrast resolution achieved with CT-IVC.

Diagnostic pitfalls with MRCP include localised signal voids caused by surgical clips and intraductal gas or blood. Bile flow voids may mimic small stones but the former are centrally placed and have less well-defined margins than stones. Acquisition times are longer for MRCP than CT-IVC and, therefore, more prone to motion and respiratory artefacts.

Endoscopic Retrograde Cholangiopancreatography

ERCP provides direct opacification of bile ducts and pancreatic ducts, with success rates of 92%–97%, and provides dynamic information during contrast medium introduction and drainage. It allows visual assessment of the duodenum and ampulla of Vater and enables biopsy and brushings, as well as interventional procedures such as sphincterotomy and stone extraction and biliary stenting and biliary stricture dilatation. Complication rates vary depending on the indication for the procedure, the presence of coexisting disease and the experience of the endoscopist, with severe complication rates of 0.9% to 2.3% and total complication rates of 8.4%–11.1%, the most common significant complication being acute pancreatitis. The main diagnostic pitfall with ERCP is the underfilling of ducts above a stricture.

Percutaneous Transhepatic Cholangiography

PTC has been substantially replaced by ERCP and MRCP. Its role now is mostly as part of transhepatic biliary intervention. A 22-G Chiba needle is used to puncture and opacify the intrahepatic ducts. Any coagulation disorder should be reversed before the procedure, which is performed with broad-spectrum IV antibiotic cover and conscious sedation or, occasionally, general anaesthesia.

Intraoperative Cholangiography

Intraoperative cholangiography (IOC) is performed routinely or selectively during cholecystectomy to detect choledocholithiasis, confirm duct stone clearance and delineate anatomy to minimise risk of bile duct injury.

T-Tube Cholangiography

If the CBD has been explored at cholecystectomy, a T-tube is usually left in place and cholangiography performed via this tube after about 7 days, before its removal. Cholangiography should confirm stone clearance and the free passage of contrast medium into the duodenum. Care must be taken to avoid the injection of air bubbles.

Hepatobiliary Scintigraphy

Hepatobiliary iminodiacetic acid (HIDA) scintigraphy uses a derivative of iminodiacetic acid, a bilirubin analogue, labelled with technetium-99m ( ^99m Tc). It is injected intravenously and serial gamma camera images are obtained over 2–4 hours. It relies on near-normal bilirubin levels, although some agents can be excreted with moderate elevations of bilirubin. Serial image acquisitions show accumulation of the isotope in the liver, bile ducts, duodenum, small bowel and gallbladder (providing it is present and the cystic duct is patent).

Endoscopic Ultrasound

Biliary endoscopic US (EUS) provides high-frequency grey-scale imaging, colour Doppler and CEUS for the evaluation of the extrahepatic biliary tree and pancreas. EUS has similar sensitivity and specificity to MRCP in diagnosing causes of biliary obstruction, being especially well suited to anatomically lower or more distal causes. Though relatively invasive, advantages are that it allows direct visualisation of the duodenum, fine-needle aspiration cytology and potentially biliary drainage. More sophisticated and expensive systems of ‘mother-daughter’ probes allow intraductal examination of the CBD, but are not routinely available.

Gallbladder Stones

The prevalence of gallbladder stones in adults in Western communities is approximately 15%. They are asymptomatic in about 80% but in this group about 15% will develop symptoms over 15 years and they confer a small lifetime risk of gallbladder carcinoma. About 70% of gallbladder stones are solely or predominantly cholesterol in type, with up to 30% being black pigment stones composed mainly of calcium bilirubinate.

Less than 10% of stones are opaque on plain radiographs, the larger stones showing laminated or peripheral calcification. On CT, a minority of gallbladder stones are visible, being hyperdense, hypodense or of mixed density.

US is the most accurate investigation for the diagnosis of gallbladder stones, which appear as echogenic foci producing acoustic shadows, and stone mobility is frequently identifiable ( Fig. 24.6 ), although is not essential for diagnosis. The sensitivity of US is greater than 95%. False-negative diagnoses are more common than false-positive ones and are usually because of small stones in patients in whom there is poor acoustic access to the gallbladder because of obesity or other unfavourable anatomy. False-negative diagnoses are reduced by careful US technique. Small stones are differentiated from small polyps by the demonstration of mobility or the presence of an acoustic shadow.

Non-visualisation of the gallbladder on US can be due to a previous cholecystectomy, non-fasting state, an abnormal gallbladder position, emphysematous cholecystitis or because the gallbladder is filled with stones. The latter can be recognised by identifying the so-called ‘double-arc shadow’ sign in the gallbladder fossa, consisting of two parallel curved echogenic lines separated by a thin anechoic space with dense acoustic shadowing distal to the deeper echogenic line ( Fig. 24.7 ).

Sludge

Sludge is commonly seen on US and appears as fine, non-shadowing dependent echoes. It is composed of calcium bilirubinate granules, cholesterol crystals and glycoproteins. It is more commonly seen in chronic fasting states, critically ill patients, those receiving total parenteral nutrition and in pregnancy. Sludge resolves spontaneously in 50% of patients and gallstones will develop in 5%–15%.

Small stones are difficult to locate within sludge, so careful imaging through sludge is important ( Fig. 24.8 ). Usually, sludge layers in a dependent fashion, but occasionally it mimics a tumour mas: that is, ‘tumefactive sludge’. Sludge can usually be differentiated from tumour by its mobility, lack of internal blood flow on Doppler examination, lack of focal gallbladder wall abnormality or lack of enhancement on CEUS.

Blood (haemobilia) and pus (empyema) may have a similar appearance to sludge, and the clinical setting aids in their differentiation. Sludge, blood and pus can also occur in the bile ducts.

Milk of Calcium Bile

Milk of calcium bile, or limy bile, is an uncommon condition in which the gallbladder bile becomes viscous, probably as a result of stasis, and contains a high concentration of calcium bilirubinate. On US, it causes diffuse echoes, similar to sludge, but is more echogenic with a tendency to layer out and produce an acoustic shadow. On CT and, occasionally, on plain radiographs, it is visible as layering high-density material.

Cholecystitis

Acute Calculous Cholecystitis

US is the best initial imaging investigation in patients with suspected acute cholecystitis, which, in 90%–95% of cases, is due to gallstones (acute calculous cholecystitis). The positive predictive values of stones combined with either tenderness localised to the gallbladder (positive sonographic Murphy sign), or the presence of a gallbladder wall thickness of >3 mm, are 92% and 95%, respectively ( Fig. 24.9 ). The negative predictive value of the absence of gallbladder stones and a negative sonographic Murphy sign is 95%. US can be definitive in about 80% of cases. Gallstone(s) may be impacted in the gallbladder neck, and this region must be carefully examined. Other US signs are gallbladder distension (diameter >5 cm), pericholecystic fluid, gallbladder wall striations and, occasionally, wall hyperaemia on Doppler examination. Fine echoes within the gallbladder may be due to sludge or pus (gallbladder empyema). If liver function tests suggest duct obstruction, a careful evaluation of the CBD should be made for choledocholithiasis.

CT is less accurate than US for acute cholecystitis, but is widely used to evaluate patients with acute abdominal pain. The CT findings in acute cholecystitis include gallbladder wall thickening, subserosal oedema, gallbladder distension, high-density bile, pericholecystic fluid and inflammatory stranding in pericholecystic fat ( Fig. 24.10 ). Gallstones are identifiable in the minority. Gallbladder wall enhancement is variable and not a reliable predictor of cholecystitis because normal gallbladders can show wall enhancement. Transient pericholecystic liver rim enhancement may be seen.

Functional studies, such as MRI with hepatobiliary contrast agents and hepatobiliary scintigraphy, assess cystic duct patency, with a positive result being absence of contrast/tracer within the gallbladder.

Gallbladder wall thickening may result from many causes other than cholecystitis. These include non-fasting state, generalised oedematous states, hepatitis, pancreatitis, gallbladder wall varices, adenomyomatosis and carcinoma, although the latter two usually cause focal rather than diffuse thickening.

Gangrenous Cholecystitis

This condition is suggested on US by pronounced irregularity or asymmetrical thickening of the gallbladder wall, internal membranous echoes resulting from sloughed mucosa and pericholecystic fluid. The clinical findings, paradoxically, may diminish with progression to gangrenous change. CT and MRI signs suggesting gangrenous cholecystitis are gas in the wall or lumen, discontinuous and/or irregular mucosal enhancement ( Fig. 24.11A ), which may also be seen on CEUS ( Fig. 24.11B ) along with internal membranes ( Fig. 24.11C ) and pericholecystic abscess. Of these, interrupted wall enhancement is the most sensitive sign (70.6%) and is highly specific (100%).

Gallbladder perforation occurs in 5%–10% of patients with acute cholecystitis and may be present as free spillage into the peritoneal cavity, a localised pericholecystic abscess, or the development of a fistula. It is suggested by pericholecystic fluid and the features of gangrenous cholecystitis, often with relative collapse of the gallbladder lumen. Localised disruption of the gallbladder wall is seen on US in 40% and on CT in 80% ( Fig. 24.12 ). CEUS can help identify perforation by showing local absence of gallbladder wall enhancement.

Emphysematous Cholecystitis

Emphysematous cholecystitis accounts for only 1% of acute cholecystitis but has a relatively high mortality rate. It is more common in men (the reverse of the usual female predominance in cholecystitis). About 50% of patients with this condition are diabetics and stones are present in less than 50%. The diagnosis may be evident on plain radiographs and is readily made on CT ( Fig. 24.13A ), which shows intramural and/or intraluminal gas caused by gas-forming organisms, while on MRI the gas appears as signal void (see Fig. 24.11C ). On US, intramural gas appears as focal or diffuse bright echogenic lines. Intraluminal gas, in the non-dependent portion of the gallbladder, causes a curvilinear, brightly echogenic band with shadowing ( Fig. 24.13B ), which can make recognition of the gallbladder difficult and lead to a false-negative US result. Small foci of intramural gas may cause ring down artefact and mimic adenomyomatosis.